Genetic Information for Testing Type 1 Diabetes GIFT-D

Genetic Information for
Testing Type 1 Diabetes
GIFT-D
Developing and
evaluating a theory-based
web education and risk
communication program
for families with T1D
New Advanced Technology to Improve the
Prediction and Prevention of Type 1 Diabetes
Massimo Trucco, P.I. - Immunology
Denise Charron-Prochownik – Behavioral Science/ Nursing
Janice S. Dorman – Genetic Epidemiology
Cathy Poole - Telemedicine
Linda M. Siminerio – Diabetes Education/ Nursing
Christopher M. Ryan – Psychology
Yvette Conley – Genetics in Nursing
Patti Schmitt – Project Director
Acknowledgement: Col. Dr. Ron Porapatich, M.D.
US Army (TATRC)
Funded by the Department of Defense
Since the completion of the Human Genome
Project and with rapid screening techniques
available, problems arise when…….
• Prediction of disease is less than perfect
• Disorder cannot be prevented/treated
• Documentation of ‘genetic disorder’ may
affect insurability and employability
• Knowing level of risk may cause psychological
distress
• People do not understand genetics (including
health professionals)
• Is genetic testing for T1D unethical?
Genome Screens for T1D
IDDM1
IDDM2
IDDM3
IDDM4
IDDM5
IDDM6
IDDM7
IDDM8
IDDM9
IDDM10
IDDM11
6p21
11p15
15q26
11q13
6q25-q27
18q21
2q31
6q27-qter
3q21-q25
10p11-q11
14q24-q31
IDDM13
IDDM15
IDDM17
IDDM18
2q34-q35
6q21
10q25
5q31-q33
1q42-qter
8q24
VDR, INFγ 12q12-qter
16p11-p13
16q22-q24
17q24-qter
TGFβ1
19p13-q13
Intervention Trials for T1D
Study
TRIGR
DIPP
Trial Net
Intervention
Avoid CM
Insulin (N)
Immunosuppr
Target /Screen
FDR / genetic
GP / genetic
FDR / antibodies
and genetic
CM = cows milk, FDR = first degree relatives,
N = nasal, GP = general population
Natural History Studies for T1D
• Conducted in the general population
• DAISY - Colorado
• PANDA - Florida
• DEW-IT - Washington
• Based on newborn genetic screening
• Concerns about proper informed consent
• Parents are notified of the results by mail
• Newborns at ‘high’ risk (~6%) recruited for
follow-up
•
Objectives of GIFT-D
Develop, implement, and evaluate
appropriate education /
communication programs about
genetic testing and type 1 diabetes
risk that can be widely
disseminated to children, parents
and health professionals
Education / Communication Programs
• Programs developed for:
• Children (unaffected siblings in T1D families)
• Parents (with an affected T1D child)
• Health care professionals (for T1D)
• Covers basic genetics, concept of genetic
susceptibility, the risk factors for T1D, and
the risk and benefits knowing one’s genetic
risk
• Decision aid to improve informed consent
• Focus is risk assessment and communication
Education / Communication Programs
Objectives
• Increase knowledge
• Improve risk perceptions
• Clarify benefits and risks of genetic
testing
• Reduce barriers
• Address ethical issues
• Facilitate decision making
• Prevent adverse reactions and minimize
distress
Genetic Testing for T1D
HLA-DQ
screening
by high
throughput
techniques
Develop an Algorithm to
Estimate an Individual’s Risk
• Permits a more ‘personalized’
approach to risk estimation than those
utilized by ongoing research projects
• Modeled after algorithm for breast
cancer developed at the University of
Pittsburgh
Photo of Risk Calculator
T1D Risk Algorithm
• Based on regression analysis from
genetic epidemiologic research
conducted by our research group
• Age
• Family history of T1D
• Sibling’s HLA-DQ genotype
• Similarity of genotype with
T1D proband’s genotype
• Translation research
T1D
~42 yrs
T1D Risk Algorithm
Age-specific probability estimates for GIFT-D
riskvar
Years
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Where:
Positive Family History
2
1
0
0.5838
0.5780
0.5721
0.5341
0.4912
0.4758
0.4705
0.4651
0.4596
0.4512
0.4426
0.3879
0.3783
0.3683
0.3480
0.3412
0.3342
0.3270
0.2828
0.1848
0.1783
0.1717
0.1649
0.1581
0.1442
0.1299
0.1003
0.0900
0.0794
0.0687
<0.0687
0.2652
0.2616
0.2580
0.2355
0.2114
0.2031
0.2003
0.1974
0.1945
0.1902
0.1857
0.1585
0.1538
0.1491
0.1396
0.1364
0.1332
0.1300
0.1103
0.0693
0.0667
0.0640
0.0614
0.0587
0.0533
0.0477
0.0365
0.0326
0.0287
0.0247
<0.0247
0.1453
0.1431
0.1410
0.1278
0.1140
0.1092
0.1076
0.1060
0.1043
0.1019
0.0994
0.0841
0.0816
0.0790
0.0737
0.0720
0.0702
0.0685
0.0578
0.0359
0.0345
0.0331
0.0317
0.0303
0.0275
0.0246
0.0187
0.0167
0.0147
0.0127
<0.0127
Negative Family History
2
1
0
0.1321
0.1302
0.1283
0.1162
0.1035
0.0992
0.0977
0.0962
0.0947
0.0925
0.0902
0.0763
0.0740
0.0716
0.0668
0.0652
0.0636
0.0620
0.0523
0.0325
0.0312
0.0300
0.0287
0.0274
0.0249
0.0223
0.0169
0.0151
0.0133
0.0114
<0.0114
0.0486
0.0479
0.0471
0.0425
0.0377
0.0360
0.0355
0.0349
0.0344
0.0335
0.0327
0.0275
0.0266
0.0258
0.0240
0.0234
0.0229
0.0223
0.0187
0.0115
0.0111
0.0106
0.0102
0.0097
0.0088
0.0079
0.0060
0.0053
0.0047
0.0040
<0.0040
0.0251
0.0247
0.0243
0.0219
0.0194
0.0185
0.0182
0.0180
0.0177
0.0172
0.0168
0.0141
0.0137
0.0132
0.0123
0.0120
0.0117
0.0114
0.0096
0.0059
0.0057
0.0054
0.0052
0.0050
0.0045
0.0040
0.0031
0.0027
0.0024
0.0021
<0.0021
A 12 year old child
who shares both DQ
haplotypes with her
T1D sister has a
~7% chance of
developing T1D by
age 30 years if
neither parent has
T1D
Risk increases to
~38% if both
Your participation in the GIFT-D pilot study is very important to us because it will help improve
our ability to predict risk for type 1 diabetes. As part of this study, we have calculated your
chance of developing type 1 diabetes. Your personalized risk estimate for developing type 1
diabetes is currently _____%. This also means that you have a _____% chance of not
developing the disease. Remember that this risk estimate does not give you a definite answer
about whether or not you will develop type 1 diabetes. It helps predict your chance of getting
the disease up to age 30.
Your personalized risk estimate was calculated using the following factors:
 Your current age
 Your family history
Whether or not you have a brother or sister with type 1 diabetes
 Your genetic makeup
Whether or not you have forms of HLA genes associated with the disease
 Your risk is not based on any environmental risk factors such as viruses or diet.
Important points about your risk for developing type 1 diabetes:
 The genetic component of your risk will not change because you cannot change what genes
you inherit.
 Genes are just one piece of the puzzle—environmental factors may also influence your risk.
Genes
Type 1
Diabetes
Environment
General information about type 1 diabetes:
 What is type 1 diabetes?
Insulin is a substance made by the pancreas that helps the body use the sugar from the food we
eat for energy. Type 1 diabetes occurs when part of the pancreas stops doing its job and
insulin is not available to help sugar enter the cells of the body.
 What are the symptoms of type 1 diabetes?
Symptoms may include: excessive thirst, frequent urination, extreme hunger, unusual weight
loss, increased fatigue, blurry vision, irritability, and vomiting/nausea. If you have any of
these symptoms, you should contact your doctor.
 How is type 1 diabetes treated?
Treatment involves daily blood sugar testing, careful dietary management, and daily insulin
injections to help the body maintain the right amount of sugar in the blood.
If you have questions in the future about the GIFT-D pilot study or your personalized risk
estimate, please call 412-624-7582.
Theory-based Genetic
Education and Risk
Communication Program:
Development & Evaluation
Genetic Education Program
Based on factors influencing behavior
(genetic testing)
Expanded Health Belief Model
•
•
•
•
•
•
Susceptibility
Severity
Benefit
Barrier
Self-efficacy
Intention
Hi! When you look in the mirror what do you see?
Do you see a girl or a boy?
Do you see eyes like your mom or dad?
Do you have hair like a brother or sister?
We see something different.
We see a person who might be a pioneer.
You may have learned about pioneers in school
who explore new lands.
You may have heard about space pioneers who go
into outer space.
We are going to tell you about becoming a health
pioneer.
Just answer the questions as we go along!
A pioneer is someone who leads the
way into the future.
Choose One:
Hi! When you look in the mirror what do you see?
Do you see a girl or a boy?
Do you see eyes like your mom or dad?
Do you have hair like a brother or sister?
We see something different.
We see a person who might be a pioneer.
You may have learned about pioneers in school who explore
new lands.
You may have heard about space pioneers who go into outer
space.
We are going to tell you about becoming a health pioneer.
Just answer the questions as we go along!
A pioneer is someone who leads the way
into the future.
Absolutely right!
Are you ready to be a pioneer?
You Chose:
Hi! When you look in the mirror what do you see?
Do you see a girl or a boy?
Do you see eyes like your mom or dad?
Do you have hair like a brother or sister?
We see something different.
We see a person who might be a pioneer.
You may have learned about pioneers in school who explore new
lands.
You may have heard about space pioneers who go into outer space.
We are going to tell you about becoming a health pioneer.
Just answer the questions as we go along!
A pioneer is someone who leads the way
into the future.
You Chose:
Nope
Remember, a pioneer is someone who does something before
other people begin doing it. A pioneer is a leader.
You might be thinking,
“How will they look inside my body? Maybe
they will use a super x-ray machine! Maybe
they have see-through body glasses that they
will wear!”
In the future this might be one way, but we
already have a way to see inside of you.
We might ask you to swish a little mouthwash
to get a little spit. Do your parents use
mouthwash for fresh breath? Or, we will take
a soft brush and rub it on the inside of your
cheek. It is safe, easy, quick and should not
hurt at all! You should only have to do it once.
Rubbing a soft brush on the inside of my
cheek is one way of getting information about
how I am like my mom or dad.
Exactly right!
Are you surprised that it is so simple?
You Chose:
Believe it or not, your spit is amazing! We can
tell all sorts of things from spit! Right now, we
want to discover one thing only. We want to see
what your genetic chance is of getting a disease
called type 1 diabetes. You know what a disease
is – it is a problem with your health, like some
people have problems breathing.
A genetic chance – do you know what that
means? To find out, let’s follow the trail of spit!
Choose One:
I will be tested to see what my chance is
for getting all kinds of diseases.
First, your spit goes to the lab where it will
be studied.
Your spit is made up of very tiny cells. Cells
are the building blocks of your body. The
cell’s job is to tell the body what to do.
Cells are to your body like bricks
are to a house.
Choose One:
We will get spit from lots of
kids! That’s a lot of spit! After
we study it, we won’t save your
spit. It has already told us the
special information we need.
You will save my spit and study it again
in the future.
Choose One:
Half of your genes come from your mom, and half from your dad.
Choose One:
Even if you have a big chance, that
doesn’t mean that you will get it.
Other things could change your
chances too, like germs, or diet, or
even things that we don’t know
about yet. We cannot tell about
everything from spit! We can only
tell your genetic chance. We are
just learning the different puzzle
pieces.
If you say that I have a big chance of
getting type 1 diabetes, then I will get it.
You Chose:
Exactly!
A chance doesn’t mean anything is definite. Genes are only
part of the puzzle.
It is interesting to learn about your
genetic chance for getting type 1
diabetes. Kids who get type 1
diabetes can get sick. Their bodies
cannot use the food they eat for
energy. They need insulin to help
their bodies get that energy. Their
pancreas has stopped making
insulin. The pancreas is an organ
like your stomach.
Choose One:
In kids with type 1 diabetes, the
pancreas has stopped working the
way it should.
Only you, your parents, and a
nurse or doctor will know your
chance of getting type 1
diabetes. Before you share what
you have learned about your
chance with others, talk to your
You Chose:
first.
I should run and tell myparents
best friend!
The answer is False.
You should talk to a parent first.
Are you ready to be a health
pioneer? If so, tell the nurse and
get ready to give up some spit!
Soon, everyone will be tested for
lots of different things. But for
now, you would be one of the first
Because of pioneers like you, we
are going to learn more about what
causes type 1 diabetes. Our goal is
to learn as much as we can, so that
no one gets this disease in the
future!
Thank-you! You have been great!
What are the risks of knowing the results of your
genetic test?
It may take some time to adjust to your test results.
Once you know your test results, you may
• feel worried, angry, or sad;
• become concerned about getting a disease that may not
develop;
• feel differently about yourself, your family, and your future;
• be upset to know that your risk is higher than the general
population for a disease that cannot be prevented.
In rare cases, insurance companies or employers may
treat people unfairly based on the results of genetic
testing.
I have read and understand the risks of getting the results of
my genetic test for type 1 diabetes.
Evaluation of Education Modules
• Outcome evaluation
• Knowledge
• Psychosocial parameters
• Behaviors
2. Process evaluation
• Time/effort
• Satisfaction
• Expectations
Measures
• Knowledge
• Diabetes
• Genetics
• Inheritance of type 1
diabetes
• Environmental risk
factors
• Psychosocial parameters
• Behaviors
• Receives genetic testing
• Receives counseling
• Prevention behavior changes
(health and/or lifestyle
related)
• (e.g. diet, seeks
prevention tx) @ 1 month
and 3 years
• Seeks other information on
the web-based resource
• Disclosure
• Anxiety
• Depression
• Perceived risk
• Process evaluation
• Health beliefs / intention
• Time / effort
• Health quality of life
• Satisfaction
• Stigma / discrimination
• Expectations
(insurance / employment)
(Control: Optimism, Religiosity,
• Family Function
Life Events...)
Develop Web-Based Format for
Education & Communication Programs
•
•
•
•
•
Broaden reach
Flexibility
Easy to use
Capture data online
Coordinated all components of the project
Genetic Education
for Health Care Professionals
Three Web-based modules:
1. Basic genetic concepts
2. Genetics of diabetes
3. Counseling issues
Continuing education online